A rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I). It is characterized by a variable clinical picture which can include dementia, psychiatric disorders, parkinsonism, dystonia, chorea, spasticity, and epilepsy¹.

Prevalence

0.2 100,000

Unknown (global), <100 families, 0.47:1,000,000 (Japanese), 0.16/100,000 (England)^2,3: 0.2/100,000. Found across ethnicities/ancestries, with population-dependent prevalence².

Age of Onset

Typical: 19-48; Range: 3-62, has second variant to delay onset⁴.

HPO Terms

–

Association

Mendelian

Locus

hg19 chr6:170870994-170871105

hg38 chr6:170561906-170562017

t2t chr6:171935458-171935569

Details

Benign range is 25-40 repeats, pathogenic range is 49+ repeats (largest to date 66 motifs, with mild correlation between size and age of onset), and intermediate alleles (41-48 repeats) are associated with reduced penetrance and potentially milder phenotypes². Huntington's disease-like phenotype⁵. CAA CAG CAA interruption is seen in all alleles stably transmitted across generations^2,6.

Mechanism

LoF/GoF

Polyglutamine expansion leading to transcriptional dysregulation⁷.

Detection

Short-read sequencing is reported to detect expansions but cannot size alleles beyond 250 bp. PCR amplification may detect expansions of ≤66 repeats [@pmid:37906407; @genereviews:NBK1438].

Year

1999⁸

Location in Gene

Coding Exon 3

Gene Strand

Alleles

Ref. Motif

CAG

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

CAG

Pathogenic (gene)

AGC

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

CAA

Interruption (gene)

AAC

gnomAD

Pathogenic genotype frequency data is not displayed for this locus because a substantial number of large alleles failed manual review by the gnomAD team.

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0011781

2genereviews:NBK1438

Profiling of Short-Tandem-Repeat Disease Alleles in 12,632 Human Whole Genomes.

Haibao,Tang, Ewen F,Kirkness, Christoph,Lippert, William H,Biggs, Martin,Fabani, Ernesto,Guzman, Smriti,Ramakrishnan, Victor,Lavrenko, Boyko,Kakaradov, Claire,Hou, Barry,Hicks, David,Heckerman, Franz J,Och, C Thomas,Caskey, J Craig,Venter, Amalio,Telenti

American journal of human genetics · 2017-11-02

pmid:29100084

4omim:607136

Huntington's disease-like phenotype due to trinucleotide repeat expansions in the TBP and JPH3 genes.

Giovanni,Stevanin, Hiroto,Fujigasaki, Anne-Sophie,Lebre, Agnes,Camuzat, Cecile,Jeannequin, Catherine,Dode, Junko,Takahashi, Chankranira,San, Robert,Bellance, Alexis,Brice, Alexandra,Durr

Brain : a journal of neurology · 2003-05-06

pmid:12805114

Comprehensive genetic diagnosis of tandem repeat expansion disorders with programmable targeted nanopore sequencing.

Igor,Stevanovski, Sanjog R,Chintalaphani, Hasindu,Gamaarachchi, James M,Ferguson, Sandy S,Pineda, Carolin K,Scriba, Michel,Tchan, Victor,Fung, Karl,Ng, Andrea,Cortese, Henry,Houlden, Carol,Dobson-Stone, Lauren,Fitzpatrick, Glenda,Halliday, Gianina,Ravenscroft, Mark R,Davis, Nigel G,Laing, Avi,Fellner, Marina,Kennerson, Kishore R,Kumar, Ira W,Deveson

Science advances · 2022-03-04

pmid:35245110

Molecular Mechanisms in Pentanucleotide Repeat Diseases.

Joana R,Loureiro, Ana F,Castro, Ana S,Figueiredo, Isabel,Silveira

Cells · 2022-01-08

pmid:35053321

A neurological disease caused by an expanded CAG trinucleotide repeat in the TATA-binding protein gene: a new polyglutamine disease?

R,Koide, S,Kobayashi, T,Shimohata, T,Ikeuchi, M,Maruyama, M,Saito, M,Yamada, H,Takahashi, S,Tsuji

Human molecular genetics · 1999-10-01

pmid:10484774

Additional Literature

Additional literature related to this locus.

Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)

Computational Short Tandem Repeat Genotyping Reveals Clinically Relevant Expansions in a Large Turkish Neurodegeneration Disease Cohort.

Zakhiriddin,Khojakulov, Robin J,Palvadeau, Müge,Kovancılar-Koç, Irmak,Atay, Irmak,Şahbaz, Şeyma,Tekgül, Ayça,Şahin, Esmer Zeynep Duru,Badakal, Tuğçe,Gül-Demirkale, Vildan,Çiftçi, Elif,Bayraktar, Ceren,Tunca, Natalia,Smolina, Fulya,Akçimen, Ayşe Nazlı,Başak

International journal of molecular sciences · 2026-05-13

pmid:42196324

Detection of short tandem repeat expansions on a targeted neurological gene panel using STRipy improves the diagnostic rate for ataxias.

Carolin K,Scriba, Chiara,Folland, Michael,Black, Jessica,Baker, Daniel,Abromeit, Samantha,Saw, Mei-Ting,Chiew, Rebecca,Gooding, Nigel G,Laing, Mark R,Davis, Gianina,Ravenscroft

Brain communications · 2026-03-16

pmid:42038259

Childhood-Onset Huntington's Disease-Like Presentation of SCA17 with Intermediate Repeats, A Case Report.

Meaghan,Berns, Kelsey,Jensen, Laura,Speltz, Leonardo Brito,Almeida

Cerebellum (London, England) · 2026-03-17

pmid:41843312

Short tandem repeat expansions in patients with neurodegenerative dementia.

Yuan,Zhu, Xuewen,Xiao, Yiliang,Liu, Zheng,Wang, Tengfei,Luo, Tianyan,Xu, Qijie,Yang, Xiaoli,Hao, Cong,Zhang, Sizhe,Zhang, Shilin,Luo, Yafang,Zhou, Xinxin,Liao, Yun,Tian, Ling,Weng, Liangjuan,Fang, Beisha,Tang, Bin,Jiao, Jinchen,Li, Lu,Shen

EBioMedicine · 2026-02-26

pmid:41762523

Non-Huntington's disease chorea: an expanding universe with acquired causes.

Francisco,Cardoso, Débora,Maia, Ricardo,Maciel, Jonathan,Carr, Taku,Hatano, Alexandra,Durr, Werner,Poewe

Brain : a journal of neurology · 2026-01-30

pmid:41612618

Repeat Variants, Biomarkers, and Molecular Signatures in Parkinson's Disease:

Jose Miguel,Laffita-Mesa, Martin,Paucar, Per,Svenningsson

International journal of molecular sciences · 2025-09-20

pmid:41009775

Diagnostic yield and limitations of whole-genome sequencing for hereditary cerebellar ataxia.

Wai Yan,Yau, Roisin,Sullivan, Emer,O'Connor, David,Pellerin, Michael H,Parkinson, Paola,Giunti, Marie-Josée,Dicaire, Matt C,Danzi, Stephan,Züchner, Bernard,Brais, Nicholas W,Wood, Henry,Houlden, Jana,Vandrovcova

Brain communications · 2025-05-17

pmid:40488180

Isolated Generalized Chorea in a Patient with Small-Expanded Allele Spinocerebellar Ataxia 17.

Giulia,Paparella, Martina,De Riggi, Simone,Aloisio, Adriana,Martini, Luca,Angelini, Daniele,Birreci, Davide,Costa, Antonio,Cannavacciuolo, Anna Maria,Griguoli, Stefano,Gambardella, Matteo,Bologna

Cerebellum (London, England) · 2025-06-06

pmid:40478462

TBP Repeat Expansion Analysis in Patients Carrying Heterozygous STUB1 Variants.

Jonathan,De Winter, Liedewei,Van de Vondel, Kristof,Van Schil, Tine,Deconinck, Katrien,Storm, Karine,Geens, Charlotte,Sommeling, David,Crosiers, Emke,Marechal, Willem,De Ridder, Peter,De Jonghe, Jonathan,Baets

Movement disorders : official journal of the Movement Disorder Society · 2025-02-14

pmid:39950762

Locus SCA17 TBP

Disease

Locus

Alleles

gnomAD

References

Additional Literature